EFFECT OF CHRONIC COCAINE TREATMENT ON MU-OPIOID AND DELTA-OPIOID RECEPTOR MESSENGER-RNA LEVELS IN DOPAMINERGICALLY INNERVATED BRAIN-REGIONS

The regulation of mu-(MOR) and delta-opioid receptor (DOR) after chron ic cocaine administration has been studied. Male Sprague-Dawley rats w ere treated for 3 days with saline and cocaine (50 mg/kg/day) delivere d by osmotic minipump. Expression of MOR and DOR mRNA in olfactory bul b, nucleus accumbens, and caudate-putamen (caudal and rostral parts) w as estimated using quantitative competitive PCR assays after reverse t ranscription. No changes in the levels of mRNA for DOR were detected a fter exposure to cocaine in the brain regions examined, A significant increase in the level of MOR mRNA was detected in nucleus accumbens af ter 3 days of cocaine treatment, In caudate-putamen and olfactory bulb , no change in MOR mRNA was observed after cocaine administration. Bot h SCH 23390 and eticlopride, selective antagonists of D1- and D2-dopam ine receptors, respectively, blocked this cocaine-induced up-regulatio n of MOR mRNA in nucleus accumbens. We suggest that endogenous opioid systems in nucleus accumbens, the brain region specifically associated with the reinforcing properties of addictive drugs, are regulated by dopaminergic mechanisms and influenced by cocaine treatment.